Rituximab in the COVID-19 era: The impact of albumin and IgG on patients with immune-mediated inflammatory diseases.

Objective: To identify factors associated with COVID-19 outcomes in patients with immune-mediated inflammatory diseases (IMID) treated with rituximab (RTX) and determine candidates for RTX administration/maintenance.

Methods: We conducted a case-control study of RTX-treated IMID patients with COVID-19 (May 2021-April 2023), including 32 hospitalized cases and 64 non-hospitalized controls matched by age, sex, IMID diagnosis. Logistic regression was used to analyze pre-COVID biochemical markers within 3-months and RTX-specific factors. Secondary outcomes in hospitalized cases included COVID-19 severity, viral shedding, and all-cause mortality.

Results: Higher RTX exposure was associated with reduced glucocorticoid dependence and higher pre-COVID albumin levels while correlated with lower IgG levels. However, lower pre-COVID albumin (OR: 0.231, p = 0.012) and higher maintenance glucocorticoid use (OR: 1.170, p = 0.007) were independently associated with hospitalization, regardless of IgG levels or RTX exposure. Among hospitalized cases, lower admission albumin (albumin_D₀; OR: 0.029, p = 0.014) predicted severe COVID-19. Patients with albumin_D₀ < 3.45 g/dL had higher mortality, regardless of IgG_D₀ or RTX timing, and experienced prolonged viral shedding despite antiviral mono-therapy. Albumin_D₀ ≥ 3.45 g/dL and IgG_D₀ ≥ 687 mg/dL were associated with the lowest mortality risk. Timing of the last RTX dose did not influence secondary outcomes.

Conclusion: Pre-COVID albumin and glucocorticoid dependence are independently associated with hospitalization regardless of RTX-specific factors. Admission albumin predicts secondary outcomes. Risk of rituximab on COVID-19 outcomes is not universal. Albumin ≥ 3.45 g/dL and IgG ≥ 687 mg/dL identify lower-risk patients, providing guidance for safer RTX administration. Key Points • Risk of rituximab on COVID-19 outcomes in immune-mediated inflammatory diseases is not universal. Serum albumin and IgG levels are critical to determine the COVID-19 outcomes. • Patients with serum albumin ≥ 3.45 g/dL and IgG ≥ 687 mg/dL demonstrate a lower risk associated with rituximab, providing guidance for its safer administration in the post-COVID-19 era amidst potential challenges from emerging infections. • Serum albumin serves as a significant prognostic marker for COVID-19 outcomes in patients receiving rituximab treatment. • The timing of the most recent rituximab infusion does not affect COVID-19 outcomes in these patients.